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The catalytic core of DEMETER guides active DNA demethylation in Arabidopsis.

  • Author(s): Zhang, Changqing
  • Hung, Yu-Hung
  • Rim, Hyun
  • Zhang, Dapeng
  • Frost, Jennifer
  • Shin, Hosub
  • Jang, Hosung
  • Liu, Fang
  • Xiao, Wenyan
  • Iyer, Lakshminarayan
  • Aravind, L
  • Zhang, Xiang-Qian
  • FISCHER, Robert L.
  • Huh, Jin
  • Hsieh, Tzung-Fu
  • et al.
Abstract

The Arabidopsis DEMETER (DME) DNA glycosylase demethylates the maternal genome in the central cell prior to fertilization and is essential for seed viability. DME preferentially targets small transposons that flank coding genes, influencing their expression and initiating plant gene imprinting. DME also targets intergenic and heterochromatic regions, but how it is recruited to these differing chromatin landscapes is unknown. The C-terminal half of DME consists of 3 conserved regions required for catalysis in vitro. We show that this catalytic core guides active demethylation at endogenous targets, rescuing dme developmental and genomic hypermethylation phenotypes. However, without the N terminus, heterochromatin demethylation is significantly impeded, and abundant CG-methylated genic sequences are ectopically demethylated. Comparative analysis revealed that the conserved DME N-terminal domains are present only in flowering plants, whereas the domain architecture of DME-like proteins in nonvascular plants mainly resembles the catalytic core, suggesting that it might represent the ancestral form of the 5mC DNA glycosylase found in plant lineages. We propose a bipartite model for DME protein action and suggest that the DME N terminus was acquired late during land plant evolution to improve specificity and facilitate demethylation at heterochromatin targets.

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